{"entity":{"id":"pakt","kind":"trial","name":"PAKT","aka":[],"tldr":"PAKT, a UK-led trial run from Barts, found that adding the AKT-blocking tablet capivasertib to paclitaxel lengthened life in metastatic triple-negative breast cancer (19 versus 13 months), most clearly in tumours with PI3K-pathway mutations. The much larger CAPItello-290 trial then found no survival gain.","summary":"PAKT (NCT02423603) was a double-blind, placebo-controlled randomised phase 2 trial sponsored by Queen Mary University of London with AstraZeneca and Cancer Research UK, which randomised 140 women with untreated metastatic triple-negative breast cancer 1 to 1 to paclitaxel 90 mg/m2 on days 1, 8 and 15 with capivasertib 400 mg or placebo twice daily on days 2 to 5, 9 to 12 and 16 to 19 of 28. Median progression-free survival was 5.9 versus 4.2 months (hazard ratio 0.74, 95 percent confidence interval 0.50 to 1.08, one-sided p 0.06 against a predefined level of 0.10) and median overall survival 19.1 versus 12.6 months (hazard ratio 0.61, 0.37 to 0.99, p 0.04). In the 28 patients with PIK3CA, AKT1 or PTEN-altered tumours median progression-free survival was 9.3 versus 3.7 months (hazard ratio 0.30, 0.11 to 0.79). Grade 3 or higher diarrhoea was 13 versus 1 percent. The trial recruited at 30 UK hospitals from Bangor and Belfast to the Royal Marsden and set up CAPItello-290, the 812-patient phase 3 with the same regimen, which in 2026 reported no overall survival difference in either the overall or the pathway-altered population.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT02423603","url":"https://clinicaltrials.gov/study/NCT02423603"},{"label":"Schmid et al., JCO 2020: capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic TNBC, the PAKT trial","url":"https://doi.org/10.1200/JCO.19.00368"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["pi3k-akt-mtor-inhibitors","cytotoxic-chemotherapy"],"targets":["akt","pik3ca","pten"],"drugs":["capivasertib","paclitaxel"],"companies":["astrazeneca"],"institutions":["cruk"],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":["nct03997123","lotus","ipatunity130"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["UK sites (registry, 30): Bangor, Belfast, Bodelwyddan, Brighton, Cambridge, Canterbury, Cardiff (Velindre), Coventry, Edinburgh, Gillingham, Glasgow (Beatson), Leeds, London (Barts, University College London Hospitals, Barking Havering and Redbridge, Guy's and St Thomas', Lewisham and Greenwich, Royal Marsden) and others."],"nct":"NCT02423603","phase":"2","setting":"Untreated metastatic triple-negative breast cancer: first-line paclitaxel with capivasertib or placebo, UK-led academic phase 2 at 30 UK hospitals and sites in France, Georgia, Hungary, Romania and South Korea","sponsor":"Queen Mary University of London, with AstraZeneca and Cancer Research UK","result":"PFS 5.9 vs 4.2 months (HR 0.74); OS 19.1 vs 12.6 months (HR 0.61, p 0.04); PIK3CA/AKT1/PTEN-altered PFS 9.3 vs 3.7 months (HR 0.30). Not confirmed by CAPItello-290.","yearReported":2020,"enrolled":140,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 71 participants (actual) for the UK registration; the JCO 2020 paper reports 140 patients randomised across the six countries.","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Capivasertib + paclitaxel","n":70,"value":5.9},{"name":"Placebo + paclitaxel","n":70,"value":4.2}],"hr":0.74,"ci":[0.5,1.08],"p":"0.06 (one-sided; predefined level 0.10)","source":"https://doi.org/10.1200/JCO.19.00368"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Capivasertib + paclitaxel","value":19.1},{"name":"Placebo + paclitaxel","value":12.6}],"hr":0.61,"ci":[0.37,0.99],"p":"0.04","source":"https://doi.org/10.1200/JCO.19.00368"},{"endpoint":"Progression-free survival, PIK3CA/AKT1/PTEN-altered tumours","unit":"months","arms":[{"name":"Capivasertib + paclitaxel","value":9.3},{"name":"Placebo + paclitaxel","value":3.7}],"hr":0.3,"ci":[0.11,0.79],"p":"0.01","source":"https://doi.org/10.1200/JCO.19.00368"}],"replication":"Not replicated: CAPItello-290 (812 patients) found overall survival 17.7 vs 18.0 months overall and 20.4 vs 20.4 months in pathway-altered tumours."},"route":"/trials/pakt/","neighbours":{"cancer":[{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","route":"/technologies/pi3k-akt-mtor-inhibitors/"}],"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"}],"drug":[{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"institution":[{"id":"cruk","kind":"institution","name":"Cancer Research UK","route":"/institutions/cruk/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"trial":[{"id":"nct03997123","kind":"trial","name":"Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC","route":"/trials/nct03997123/"},{"id":"ipatunity130","kind":"trial","name":"IPATunity130","route":"/trials/ipatunity130/"},{"id":"lotus","kind":"trial","name":"LOTUS","route":"/trials/lotus/"}]}}